کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1357764 981276 2015 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design and synthesis of novel quinoline–aminopiperidine hybrid analogues as Mycobacterium tuberculosis DNA gyraseB inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Design and synthesis of novel quinoline–aminopiperidine hybrid analogues as Mycobacterium tuberculosis DNA gyraseB inhibitors
چکیده انگلیسی

Antibiotics with good therapeutic value and novel mechanism of action are becoming increasingly important in today’s battle against bacterial resistance. One of the popular targets being DNA gyrase, is currently becoming well-established and clinically validated for the development of novel antibacterials. In the present work, a series of forty eight quinoline–aminopiperidine based urea and thiourea derivatives were synthesized as pharmacophoric hybrids and evaluated for their biological activity. Compound, 1-(4-chlorophenyl)-3-(1-(6-methoxy-2-methylquinolin-4-yl)piperidin-4-yl)thiourea (45) was found to exhibit promising in vitro Mycobacterium smegmatis GyrB IC50 of 0.95 ± 0.12 μM and a well correlated Mycobacterium tuberculosis (MTB) DNA gyrase supercoiling IC50 of 0.62 ± 0.16 μM. Further, compound 45 also exhibited commendable MTB MIC, safe eukaryotic cytotoxic profile with no signs of cardiotoxicity in zebrafish ether-a-go-go-related gene (zERG).

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 23, Issue 9, 1 May 2015, Pages 2062–2078
نویسندگان
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